Modes of therapeutic delivery in synthetic microbiology

Trends Microbiol. 2023 Feb;31(2):197-211. doi: 10.1016/j.tim.2022.09.003. Epub 2022 Oct 8.

Abstract

For decades, bacteria have been exploited as vectors for vaccines and therapeutics. However, the bacterial arsenal used has historically been limited to a few strains. Advancements in immunology, combined with the development of genetic tools, have expanded our strategies and capabilities to engineer bacteria using various delivery strategies. Depending on the application, each delivery strategy requires specific considerations, optimization, and safety concerns. Here, we review various modes of therapeutic delivery used to target or vaccinate against a variety of ailments in preclinical models and in clinical trials. We highlight modes of bacteria-derived delivery best suited for different applications. Finally, we discuss current obstacles in bacteria-derived therapies and explore potential improvements of the various modes of therapeutic delivery.

Trial registration: ClinicalTrials.gov NCT02853604 NCT03234465 NCT03751007.

Keywords: bacterial-derived biotherapeutics; cell lysis; live biotherapeutic products; membrane vesicles and bacterial ghosts; secretion; surface display.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacteria* / genetics

Associated data

  • ClinicalTrials.gov/NCT02853604
  • ClinicalTrials.gov/NCT03234465
  • ClinicalTrials.gov/NCT03751007